^(131)I标记的甲状腺未分化癌人源单链抗体在荷瘤裸鼠模型的放射免疫显像  

Radioimmunoimaging of ^(131)I Labeled Human sc Fv Against Anaplastic Thyroid Carcinoma in Tumor Bearing Nude Mice

作　　者：刘倩[1] 刘琼[1] 李文波[1] 许璐[1] 周静[1] 刘影[1] 庞华[1] 

机构地区：[1]重庆医科大学附属第一医院核医学科,重庆400016

出　　处：《中国医学影像学杂志》2017年第5期321-324,共4页Chinese Journal of Medical Imaging

基　　金：国家自然科学基金(81071171);重庆市科技计划面上项目(CSCT2013JCYJA10072);国家临床重点专科建设项目(国卫办医函[2013]544号)

摘　　要：目的测定^(131)I标记的甲状腺未分化癌(ATC)人源单链抗体(scFv)的放射性纯度与比活度,并探讨其在荷瘤裸鼠模型的体内分布情况和放射免疫显像特点,以期为ATC的诊断及治疗提供一种新的方法。材料与方法接种ATC细胞构建荷人ATC裸鼠模型。采用氯胺T法实现scFv的^(131)I标记,Sephadex G25M柱纯化标记抗体,采用三氯醋酸法测定其标记率,采用纸层析法测定^(131)I标记scFv的放化纯度、室温稳定性及血清稳定性。荷瘤裸鼠尾静脉注射^(131)I-scFv后12、24、48、72 h取各组织器官分析^(131)I-scv在体内组织器官中的生物分布情况,另取荷瘤裸鼠尾静脉注射^(131)I-scFv后12、24、48、72 h进行SPECT静态显像,观察瘤内放射性浓聚,待肿瘤清晰显影,进行SPECT/CT图像融合。结果纯化后的^(131)I-scFv标记率为91.64%,放化纯度为(93.3±0.3)%;^(131)I-scFv放于室温及血清孵育1、6、12、24 h后所测得放射性化学纯度均高于90%。^(131)I-scFv在肿瘤组织、肝、肾、肠、血液中具有较高的放射性分布。SPECT显示^(131)I-scFv能够在肿瘤组织中选择性浓聚,肿瘤组织靶/非靶比值在48 h时达最高为4.38,且显影最清晰。结论成功制备^(131)I-scFv,^(131)I-scFv在荷瘤裸鼠模型中有较好的显像效果,为进一步开展ATC的诊断及治疗研究奠定基础。Purpose To study the radioactive purity and activity of ^131I labeled human single chain variable fragments antibodies （scFv） against anaplastic thyroid carcinoma （ATC）, and to explore its distribution and radioimmunoirnaging characteristics in tumor bearing nude mice model in vivo so as to provide a new method for anaplastic thyroid carcinoma diagnosis and treatment. Materials and Methods The nude mice model bearing human anaplastic thyroid carcinoma was constructed. The chloramine T method was used to label scFv with ^131I and the Sephadex G25M was used for purification of labeled scFv. Labeling rate was determined by trichloroacetic acid method; radiochemical purity, room temperature stability and serum stability were examined using paper chromatography.^131I-scFv was injected via tail vein in mice, and the distribution of ^131I-scFv in body tissues and organs was analyzed at 12, 24, 48, 72 h after injection. Static SPECT imaging was performed at 12, 24, 48, 72 h after injection to observe the intratumoral accumulation of radioactivity. The SPECT/CT image fusion was performed when the tumor tissues were clearly visible. Results ml-scFv was purified, and the labeling rate was 91.64%; the radiochemical purity was （93.3±0.3）%. The radiochemical purity of ^131I-scFv placed at room temperature and the serum for 1, 6, 12, 24 h were all 〉90%. The radioactive distribution of ^131I-scFv in tumor, liver, kidney, intestine and blood was high. SPECT imaging showed ^131I-scFv was selectively concentrated in tumor tissue; the target/non-target ratio was the highest at 48 h, and the imaging was most satisfactory. Conclusion ^131I-scFv can be successfully prepared. SPECT imaging of ^131I-scFv in nude mice model is satisfactory, which lays the foundation for further research in ATC diagnosis and treatment.

关 键 词：甲状腺肿瘤 癌 碘放射性同位素 单链抗体 放射免疫显像 体层摄影术 发射型计算机 单光子 体层摄影术 X线计算机 疾病模型 动物 小鼠 裸 

分 类 号：R445.5[医药卫生—影像医学与核医学] R736.1[医药卫生—诊断学]